Numerous studies have documented that medications which increase brain 5-HT, such as fenfluramine, are effective anorectic agents which help obese patients lose weight and which also decrease craving for sweets and carbohydrates (6,23). Evidence from other studies also indicate that increases in brain 5-HT may help decrease craving for alcohol and cocaine (1,8,14,15,18-20,24). 5-hydroxy-L-tryptophan, abbreviated 5-HTP, is the immediate precursor of serotonin (5-HT). A goal of treatment with 5-HTP is to increase brain 5-HT. Previous studies in animals and humans have established that administration of 5-HTP increases brain 5-HT (7,13,21). However, 5-HTP administered systemically (intraperitoneal, oral, intravenous) is rapidly converted to 5-HT by an enzyme called peripheral decarboxylase before it ever gets into the brain. Thus, to achieve the desired effect of increasing brain 5-HT it is necessary to co-administer an inhibitor of the enzyme peripheral decarboxylase along with the 5-HTP. A typical means of doing so is to administer carbidopa along with the 5-HTP.
Increases in synaptic 5-HT decreases the firing rate of 5-HT neurons via stimulation of inhibitory 5-HT1a receptors located on the cell bodies in the raphe. This serves as a negative feedback loop. Administration of 5-HT1a receptor antagonists interrupt this feedback loop, and thereby increase the ability of 5-HT reuptake inhibitors to increase synaptic 5-HT (5,9,17). The clinically available beta adreneric receptor antagonist medication pindolol is also a 5-HT1a antagonist, and can be used to increase the ability of 5-HTP to increase brain 5-HT (4,12).